376 research outputs found

    Towards freeform curved blazed gratings using diamond machining.

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    Concave blazed gratings greatly simplify the architecture of spectrographs by reducing the number of optical components. The production of these gratings using diamond-machining offers practically no limits in the design of the grating substrate shape, with the possibility of making large sag freeform surfaces unlike the alternative and traditional method of holography and ion etching. In this paper, we report on the technological challenges and progress in the making of these curved blazed gratings using an ultra-high precision 5 axes Moore-Nanotech machine. We describe their implementation in an integral field unit prototype called IGIS (Integrated Grating Imaging Spectrograph) where freeform curved gratings are used as pupil mirrors. The goal is to develop the technologies for the production of the next generation of low-cost, compact, high performance integral field unit spectrometers

    SUMO chain formation is required for response to replication arrest in S. pombe

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    SUMO is a ubiquitin-like protein that is post-translationally attached to one or more lysine residues on target proteins. Despite having only 18% sequence identity with ubiquitin, SUMO contains the conserved betabetaalphabetabetaalphabeta fold present in ubiquitin. However, SUMO differs from ubiquitin in having an extended N-terminus. In S. pombe the N-terminus of SUMO/Pmt3 is significantly longer than those of SUMO in S. cerevisiae, human and Drosophila. Here we investigate the role of this N-terminal region. We have used two dimensional gel electrophoresis to demonstrate that S. pombe SUMO/Pmt3 is phosphorylated, and that this occurs on serine residues at the extreme N-terminus of the protein. Mutation of these residues (in pmt3-1) results in a dramatic reduction in both the levels of high Mr SUMO-containing species and of total SUMO/Pmt3, indicating that phosphorylation of SUMO/Pmt3 is required for its stability. Despite the significant reduction in high Mr SUMO-containing species, pmt3-1 cells do not display an aberrant cell morphology or sensitivity to genotoxins or stress. Additionally, we demonstrate that two lysine residues in the N-terminus of S. pombe SUMO/Pmt3 (K14 and K30) can act as acceptor sites for SUMO chain formation in vitro. Inability to form SUMO chains results in aberrant cell and nuclear morphologies, including stretched and fragmented chromatin. SUMO chain mutants are sensitive to the DNA synthesis inhibitor, hydroxyurea (HU), but not to other genotoxins, such as UV, MMS or CPT. This implies a role for SUMO chains in the response to replication arrest in S. pomb

    Directly Imaging Rocky Planets from the Ground

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    Over the past three decades instruments on the ground and in space have discovered thousands of planets outside the solar system. These observations have given rise to an astonishingly detailed picture of the demographics of short-period planets, but are incomplete at longer periods where both the sensitivity of transit surveys and radial velocity signals plummet. Even more glaring is that the spectra of planets discovered with these indirect methods are either inaccessible (radial velocity detections) or only available for a small subclass of transiting planets with thick, clear atmospheres. Direct detection can be used to discover and characterize the atmospheres of planets at intermediate and wide separations, including non-transiting exoplanets. Today, a small number of exoplanets have been directly imaged, but they represent only a rare class of young, self-luminous super-Jovian-mass objects orbiting tens to hundreds of AU from their host stars. Atmospheric characterization of planets in the <5 AU regime, where radial velocity (RV) surveys have revealed an abundance of other worlds, is technically feasible with 30-m class apertures in combination with an advanced AO system, coronagraph, and suite of spectrometers and imagers. There is a vast range of unexplored science accessible through astrometry, photometry, and spectroscopy of rocky planets, ice giants, and gas giants. In this whitepaper we will focus on one of the most ambitious science goals --- detecting for the first time habitable-zone rocky (<1.6 R_Earth) exoplanets in reflected light around nearby M-dwarfsComment: 8 pages, 1 figure, Astro2020 Science White Pape

    Expression, regulation and clinical significance of soluble and membrane CD14 receptors in pediatric inflammatory lung diseases

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    <p>Abstract</p> <p>Background</p> <p>Inflammatory lung diseases are a major morbidity factor in children. Therefore, novel strategies for early detection of inflammatory lung diseases are of high interest. Bacterial lipopolysaccharide (LPS) is recognized via Toll-like receptors and CD14. CD14 exists as a soluble (sCD14) and membrane-associated (mCD14) protein, present on the surface of leukocytes. Previous studies suggest sCD14 as potential marker for inflammatory diseases, but their potential role in pediatric lung diseases remained elusive. Therefore, we examined the expression, regulation and significance of sCD14 and mCD14 in pediatric lung diseases.</p> <p>Methods</p> <p>sCD14 levels were quantified in serum and bronchoalveolar lavage fluid (BALF) of children with infective (pneumonia, cystic fibrosis, CF) and non-infective (asthma) inflammatory lung diseases and healthy control subjects by ELISA. Membrane CD14 expression levels on monocytes in peripheral blood and on alveolar macrophages in BALF were quantified by flow cytometry. <it>In vitro </it>studies were performed to investigate which factors regulate sCD14 release and mCD14 expression.</p> <p>Results</p> <p>sCD14 serum levels were specifically increased in serum of children with pneumonia compared to CF, asthma and control subjects. <it>In vitro</it>, CpG induced the release of sCD14 levels in a protease-independent manner, whereas LPS-mediated mCD14 shedding was prevented by serine protease inhibition.</p> <p>Conclusions</p> <p>This study demonstrates for the first time the expression, regulation and clinical significance of soluble and membrane CD14 receptors in pediatric inflammatory lung diseases and suggests sCD14 as potential marker for pneumonia in children.</p

    Expression, regulation and clinical significance of soluble and membrane CD14 receptors in pediatric inflammatory lung diseases

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    <p>Abstract</p> <p>Background</p> <p>Inflammatory lung diseases are a major morbidity factor in children. Therefore, novel strategies for early detection of inflammatory lung diseases are of high interest. Bacterial lipopolysaccharide (LPS) is recognized via Toll-like receptors and CD14. CD14 exists as a soluble (sCD14) and membrane-associated (mCD14) protein, present on the surface of leukocytes. Previous studies suggest sCD14 as potential marker for inflammatory diseases, but their potential role in pediatric lung diseases remained elusive. Therefore, we examined the expression, regulation and significance of sCD14 and mCD14 in pediatric lung diseases.</p> <p>Methods</p> <p>sCD14 levels were quantified in serum and bronchoalveolar lavage fluid (BALF) of children with infective (pneumonia, cystic fibrosis, CF) and non-infective (asthma) inflammatory lung diseases and healthy control subjects by ELISA. Membrane CD14 expression levels on monocytes in peripheral blood and on alveolar macrophages in BALF were quantified by flow cytometry. <it>In vitro </it>studies were performed to investigate which factors regulate sCD14 release and mCD14 expression.</p> <p>Results</p> <p>sCD14 serum levels were specifically increased in serum of children with pneumonia compared to CF, asthma and control subjects. <it>In vitro</it>, CpG induced the release of sCD14 levels in a protease-independent manner, whereas LPS-mediated mCD14 shedding was prevented by serine protease inhibition.</p> <p>Conclusions</p> <p>This study demonstrates for the first time the expression, regulation and clinical significance of soluble and membrane CD14 receptors in pediatric inflammatory lung diseases and suggests sCD14 as potential marker for pneumonia in children.</p

    The Inertio-Elastic Planar Entry Flow of Low-Viscosity Elastic Fluids in Micro-fabricated Geometries

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    The non-Newtonian flow of dilute aqueous polyethylene oxide (PEO) solutions through microfabricated planar abrupt contraction-expansions is investigated. The contraction geometries are fabricated from a high-resolution chrome mask and cross-linked PDMS gels using the tools of soft-lithography. The small length scales and high deformation rates in the contraction throat lead to significant extensional flow effects even with dilute polymer solutions having time constants on the order of milliseconds. The dimensionless extra pressure drop across the contraction increases by more than 200% and is accompanied by significant upstream vortex growth. Streak photography and videomicroscopy using epifluorescent particles shows that the flow ultimately becomes unstable and three-dimensional. The moderate Reynolds numbers (0.03 ⤠Re ⤠44) associated with these high Deborah number (0 ⤠De ⤠600) microfluidic flows results in the exploration of new regions of the Re-De parameter space in which the effects of both elasticity and inertia can be observed. Understanding such interactions will be increasingly important in microfluidic applications involving complex fluids and can best be interpreted in terms of the elasticity number, El = De/Re, which is independent of the flow kinematics and depends only on the fluid rheology and the characteristic size of the device.NS

    An investigation of the three-way joint coaching alliance: a social identity theory perspective

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    This study builds upon the previous research that recognised coaching as a triangular political space generating power relationships. We integrate social identity theory into this power negotiation process and consider that the ultimate purpose of coaching is to facilitate a shared coaching identity among all related collaborators. To gain in-depth understanding of factors that promote a three-way joint coaching identity; we conducted 25 critical incident interviews and two levels of Q-sorting (n = 10) with coaches, coachees and organisational stakeholders. The research results indicated that a workplace coaching identity is a flexible space underpinned by coaches’ attitude, all collaborators’ positions and the contracting process. Coaches’ accommodated communication techniques determine the relationship climate (instrumental or influential). Coaches’ position in the coaching space regulates their self-interests and motivation to change. Moreover, a transparent contracting process encourages communication flows and psychological exchanges among all collaborators that may gain more support from stakeholders

    Intestinal Inflammation Responds to Microbial Tissue Load Independent of Pathogen/Non-Pathogen Discrimination

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    The intestinal immune system mounts inflammatory responses to pathogens but tolerates harmless commensal microbiota. Various mechanisms for pathogen/non-pathogen discrimination have been proposed but their general relevance for inflammation control is unclear. Here, we compared intestinal responses to pathogenic Salmonella and non-pathogenic E. coli. Both microbes entered intestinal Peyer’s patches and, surprisingly, induced qualitatively and quantitatively similar initial inflammatory responses revealing a striking discrimination failure. Diverging inflammatory responses only occurred when Salmonella subsequently proliferated and induced escalating neutrophil infiltration, while harmless E. coli was rapidly cleared from the tissue and inflammation resolved. Transient intestinal inflammation induced by harmless E. coli tolerized against subsequent exposure thereby preventing chronic inflammation during repeated exposure. These data revealed a striking failure of the intestinal immune system to discriminate pathogens from harmless microbes based on distinct molecular signatures. Instead, appropriate intestinal responses to gut microbiota might be ensured by immediate inflammatory responses to any rise in microbial tissue loads, and desensitization after bacterial clearance
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